2. AP Biology 2006-2007 Human Genetic Diseases 12 3456

3. AP Biology Pedigree analysis Pedigree analysis reveals Mendelian patterns in human inheritance  data mapped on a family tree = male= female= male w/ trait = female w/ trait

4. AP Biology Simple pedigree analysis 12 3456 12 3456 What’s the likely inheritance pattern?

5. AP Biology Genetic counseling Pedigree can help us understand the past & predict the future Thousands of genetic disorders are inherited as simple recessive traits  from benign conditions to deadly diseases albinism cystic fibrosis Tay sachs sickle cell anemia PKU

6. AP Biology Genetic testing sequence individual genes

7. AP Biology Recessive diseases The diseases are recessive because the allele codes for either a malfunctioning protein or no protein at all  Heterozygotes (Aa) carriers have a normal phenotype because one “normal” allele produces enough of the required protein

8. AP Biology Heterozygote crosses Aa x Aa Aa male / sperm A a female / eggs AA Aaaa Aa A a A a AAAaaaAa Heterozygotes as carriers of recessive alleles carrier disease

9. AP Biology Cystic fibrosis (recessive) Primarily whites of European descent  strikes 1 in 2500 births 1 in 25 whites is a carrier (Aa)  normal allele codes for a membrane protein that transports Cl - across cell membrane defective or absent channels limit transport of Cl - & H 2 O across cell membrane thicker & stickier mucus coats around cells mucus build-up in the pancreas, lungs, digestive tract & causes bacterial infections  without treatment children die before 5; with treatment can live past their late 20s normal lung tissue

10. AP Biology Effect on Lungs Chloride channel transports salt through protein channel out of cell Osmosis: H 2 O follows Cl – airway Cl – H2OH2O H2OH2O mucus secreting glands bacteria & mucus build up thickened mucus hard to secrete normal lungs cystic fibrosis cells lining lungs Cl – channel

11. AP Biology loss of one amino acid delta F508

12. AP Biology Tay-Sachs (recessive) Primarily Jews of eastern European (Ashkenazi) descent & Cajuns (Louisiana)  strikes 1 in 3600 births 100 times greater than incidence among non-Jews  non-functional enzyme fails to breakdown lipids in brain cells fats collect in cells destroying their function symptoms begin few months after birth seizures, blindness & degeneration of muscle & mental performance child usually dies before 5yo

13. AP Biology Sickle cell anemia (recessive) Primarily Africans  strikes 1 out of 400 African Americans high frequency  caused by substitution of a single amino acid in hemoglobin  when oxygen levels are low, sickle-cell hemoglobin crystallizes into long rods deforms red blood cells into sickle shape sickling creates pleiotropic effects = cascade of other symptoms

14. AP Biology Sickle cell anemia Substitution of one amino acid in polypeptide chain hydrophilic amino acid hydrophobic amino acid

15. AP Biology

16. Sickle cell phenotype 2 alleles are codominant  both normal & mutant hemoglobins are synthesized in heterozygote (Aa)  50% cells sickle; 50% cells normal  carriers usually healthy  sickle-cell disease triggered under blood oxygen stress exercise

17. AP Biology Heterozygote advantage Malaria  single-celled eukaryote parasite spends part of its life cycle in red blood cells In tropical Africa, where malaria is common:  homozygous dominant individuals die of malaria  homozygous recessive individuals die of sickle cell anemia  heterozygote carriers are relatively free of both reproductive advantage High frequency of sickle cell allele in African Americans is vestige of African roots

18. AP Biology Prevalence of Malaria Prevalence of Sickle Cell Anemia

19. AP Biology Huntington’s chorea (dominant) Dominant inheritance  repeated mutation on end of chromosome 4 mutation = CAG repeats glutamine amino acid repeats in protein one of 1 st genes to be identified  build up of “huntingtin” protein in brain causing cell death memory loss muscle tremors, jerky movements  “chorea” starts at age 30-50 early death  10-20 years after start 1872 Testing… Would you want to know?

20. AP Biology Genetics & culture Why do all cultures have a taboo against incest?  laws or cultural taboos forbidding marriages between close relatives are fairly universal Fairly unlikely that 2 unrelated carriers of same rare harmful recessive allele will meet & mate  but matings between close relatives increase risk “consanguineous” (same blood) matings  individuals who share a recent common ancestor are more likely to carry same recessive alleles

21. AP Biology AAAaaaAa A hidden disease reveals itself AA x Aa AA male / sperm A a female / eggs AaAAAaAAAa x Aa male / sperm A a female / eggs AAAaaaAa increase carriers in population hidden disease is revealed

22. AP Biology 2006-2007 Any questions?

23. AP Biology 2006-2007 Ghosts of Lectures Past (storage)

24. AP Biology Heterozygote advantage Sickle cell frequency  high frequency of heterozygotes is unusual for allele with severe detrimental effects in homozygotes 1 out of 400 African Americans Suggests some selective advantage of being heterozygous  sickle cell: resistance to malaria?  cystic fibrosis: resistance to cholera?

25. AP Biology Malaria

26. AP Biology Woody Guthrie & Arlo Guthrie